F. Mauro

Development of a set of nomograms to predict acute lower gastrointestinal toxicity for prostate cancer 3D-CRT.

PURPOSE To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. METHODS AND MATERIALS Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. RESULTS Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p = 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR = 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR = 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p = 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR = 1.029). CONCLUSIONS To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.

Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

PURPOSE Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. METHODS AND MATERIALS This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). RESULTS Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. CONCLUSIONS We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patients characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.

Long term rectal function after high-dose prostatecancer radiotherapy: Results from a prospective cohort study

PURPOSE To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors. MATERIALS AND METHODS Questionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up ≥6 years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3 years after RT was also investigated. RESULTS Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2-G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p=0.016) ≥G1 lrb was significantly associated with V75 Gy (OR=1.07). In multivariate analysis, ≥G1 linc was associated with V40 Gy (OR=1.015), use of antihypertensive medication (OR=0.38), abdominal surgery before RT (OR=4.7), haemorrhoids (OR=2.6), and G2-G3 acute faecal incontinence (OR=4.4), a nomogram to predict the risk of long-term ≥G1 linc was proposed. Importantly, the prevalence of ≥G1 linc was significantly correlated with the mean incontinence score during the first 3 years after RT (OR=16.3). CONCLUSIONS Long-term (median: 7 years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3 years after RT. Linc was associated with several risk factors.